ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1652G>T (p.Cys551Phe)

dbSNP: rs1554297409
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000584346 SCV000691039 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces cysteine with phenylalanine at codon 551 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001340306 SCV001534107 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-09-10 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 492266). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 551 of the PMS2 protein (p.Cys551Phe).
Ambry Genetics RCV000584346 SCV002704684 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-11 criteria provided, single submitter clinical testing The p.C551F variant (also known as c.1652G>T), located in coding exon 11 of the PMS2 gene, results from a G to T substitution at nucleotide position 1652. The cysteine at codon 551 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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